Hassan Mohammad Q, Tye Coralee E, Stein Gary S, Lian Jane B
Department of Oral & Maxillofacial Surgery, School of Dentistry, The University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, VT, USA.
Bone. 2015 Dec;81:746-756. doi: 10.1016/j.bone.2015.05.026. Epub 2015 May 31.
Non-coding RNAs (ncRNAs) have evolved in eukaryotes as epigenetic regulators of gene expression. The most abundant regulatory ncRNAs are the 20-24 nt small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs, <200 nt). Each class of ncRNAs operates through distinct mechanisms, but their pathways to regulating gene expression are interrelated in ways that are just being recognized. While the importance of lncRNAs in epigenetic control of transcription, developmental processes and human traits is emerging, the identity of lncRNAs in skeletal biology is scarcely known. However, since the first profiling studies of miRNA at stages during osteoblast and osteoclast differentiation, over 1100 publications related to bone biology and pathologies can be found, as well as many recent comprehensive reviews summarizing miRNA in skeletal cells. Delineating the activities and targets of specific miRNAs regulating differentiation of osteogenic and resorptive bone cells, coupled with in vivo gain- and loss-of-function studies, discovered unique mechanisms that support bone development and bone homeostasis in adults. We present here "guiding principles" for addressing biological control of bone tissue formation by ncRNAs. This review emphasizes recent advances in understanding regulation of the process of miRNA biogenesis that impact on osteogenic lineage commitment, transcription factors and signaling pathways. Also discussed are the approaches to be pursued for an understanding of the role of lncRNAs in bone and the challenges in addressing their multiple and complex functions. Based on new knowledge of epigenetic control of gene expression to be gained for ncRNA regulation of the skeleton, new directions for translating the miRNAs and lncRNAs into therapeutic targets for skeletal disorders are possible. This article is part of a Special Issue entitled Epigenetics and Bone.
非编码RNA（ncRNAs）在真核生物中作为基因表达的表观遗传调控因子而进化。最丰富的调控性ncRNAs是20 - 24个核苷酸的小微小RNA（miRNAs）和长链非编码RNA（lncRNAs，<200个核苷酸）。每一类ncRNAs都通过不同的机制发挥作用，但其调控基因表达的途径以刚刚被认识的方式相互关联。虽然lncRNAs在转录的表观遗传控制、发育过程和人类性状中的重要性正在显现，但lncRNAs在骨骼生物学中的身份却鲜为人知。然而，自首次在成骨细胞和破骨细胞分化阶段对miRNA进行谱分析研究以来，可发现超过1100篇与骨生物学和病理学相关的出版物，以及许多近期总结骨骼细胞中miRNA的全面综述。描绘调控成骨和骨吸收性骨细胞分化的特定miRNAs的活性和靶标，再结合体内功能获得和功能丧失研究，发现了支持成人骨骼发育和骨稳态的独特机制。我们在此提出关于解决ncRNAs对骨组织形成的生物学控制的“指导原则”。本综述强调了在理解影响成骨谱系定向、转录因子和信号通路的miRNA生物发生过程调控方面的最新进展。还讨论了为理解lncRNAs在骨中的作用而应采用的方法以及应对其多种复杂功能的挑战。基于通过ncRNA对骨骼的调控而获得的基因表达表观遗传控制的新知识，将miRNAs和lncRNAs转化为骨骼疾病治疗靶点的新方向成为可能。本文是名为“表观遗传学与骨骼”的特刊的一部分。
